Method and system for in-vivo temperature measurement based on AC magnetization of magnetic nanoparticle

ABSTRACT

The invention discloses a method for in-vivo temperature measurement based on AC magnetization of magnetic nanoparticles, and relates to a nano test technology field. The invention positions magnetic nano agent at an area of a measured object, applies an AC excitation magnetic field to the area of the magnetic nano agent, collects an AC magnetization signal of the magnetic nano agent under the AC excitation magnetic field, detects amplitudes of odd harmonics of the AC magnetization signal, and finally calculates in-vivo temperature according to a relationship between the odd harmonics and the in-vivo temperature. The invention predetermines the relationship between the odd harmonics and the in-vivo temperature via the discrete Langevin&#39;s function and the Fourier transformation, solves the in-vivo temperature according to the relationship without considering concentration of the magnetic nanoparticles, and effective moment as temperature varies, and thus accurately detecting the in-vivo temperature.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is the US national stage of InternationalApplication PCT/CN2013/077917 filed on Jun. 25, 2013 which, in turn,claims priority to Chinese Patent Application CN2013100658967 filed onMar. 1, 2013.

FIELD OF THE INVENTION

The invention relates to a nano test technology field, and moreparticularly to a method and a system for in-vivo temperaturemeasurement based on AC magnetization of magnetic nanoparticles.

BACKGROUND OF THE INVENTION

In-vivo temperature refers to temperature of tissues in complete andsurvival individuals. In the biological and medical field, in-vivotemperature measurement methods are divided into invasive measurementand noninvasive measurement. The invasive measurement method is simple,real-time and accurate, and it is convenient to monitor measurementpositions by videos. However, problems with the method are that, woundcaused by the method is comparatively large, insertion of probes oftenleads to metastasis of pathological cells, interaction between radiationfields of heating sources and the probes reduces measurement accuracy,and measured temperature is temperature at a certain point, nottemperature distribution over a whole coagulation area. The noninvasivetemperature measurement method is now widely accepted and used in themedical field as being capable of effectively preventing infection ofwound or expansion of cancer cell, and of providing real-timeinformation of in-vivo temperature and temperature (field) distributionimages deeply in tissues with comparatively high accuracy.

Presently, the noninvasive temperature measurement method comprises aultrasound temperature measurement method, a microwave temperaturemeasurement method, a nuclear magnetic resonance (NMR) temperaturemeasurement method, a remote magnetic nanoparticle measurement methodand so on.

Limited by size of organisms, the ultrasound temperature measurementmethod employs reflection echo, and a disadvantages thereof is that itmust measure sound and temperature characteristics of different tissuesin advance, but temperature characteristics of the tissues issignificantly different and unstable. The microwave temperaturemeasurement method can only be used to tumor at superficial layers, andresolution is to be significantly reduced at deep layers. However, thismethod must predetermine temperature distribution and measure structureand electrical parameters of organisms, this is because that thermalnoise microwave measured at body surface is related to temperaturedistribution, structure of tissues and electrical properties within ameasurement range. Problems with the NMR temperature measurement methodare that it is too expensive to be widely used, spatial and temperatureresolution thereof are limited, and more importantly, it can only obtainvariation in temperature, not absolute temperature of tissues. A remotenoninvasive temperature measurement method using magnetic nanoparticlesis a high-accuracy temperature (field) measurement technique deeply intissues being capable of addressing the above-mentioned problems. Thismethod implements measurement and control of in-vivo temperature, andthus being capable of assessing and adjusting hyperthermia treatment oftumor in real time at a molecular level. In addition, a magneticparticle imaging (MPI) based on magnetic nanoparticles features anextremely high real-time rate in remote noninvasive in-vivo temperaturemeasurement. Superior to a traditional noninvasive method for in-vivotemperature measurement—NMR, the MPI system is more simple,cost-effective and accurate, and generates pixels by changingmagnetization of the magnetic nanoparticles whereby enabling the systemto have high temperature sensibility. Therefore, the MPI is capable ofmeasuring and imaging the in-vivo temperature in theory.

Temperature-related attributes of the magnetic nanoparticle comprise aparticle size, saturated magnetic moment, concentration distributionthereof in the organism, and so on. The particle size and the saturatedmagnetic moment can be determined via repeated test outside theorganism, but it is difficult to measure concentration of the magneticnanoparticle in the organism, and no measurement method is available atpresent. Meanwhile, uncertainty of concentration and spatialdistribution of the magnetic nanoparticle in the organism is to cause asignificant error in the in-vivo temperature measurement. To summarize,to facilitate remote temperature measurement without knowingconcentration of the magnetic nanoparticle has become an unsolvedproblem in magnetic nano hyperthermia treatment of tumor.

SUMMARY OF THE INVENTION

In view of the above-mentioned problems, it is an objective of theinvention to provide a method for in-vivo temperature measurement basedon AC magnetization of magnetic nanoparticles that is capable ofaccurately measuring in-vivo temperature without obtaining concentrationof the magnetic nanoparticles.

A method for in-vivo temperature measurement, comprising steps of:

(1) positioning magnetic nano agent at an area of a measured object;

(2) applying an AC excitation magnetic field to the area of the magneticnano agent;

(3) collecting an AC magnetization signal of the magnetic nano agentunder the AC excitation magnetic field;

(4) detecting amplitudes C₁, C₃, . . . , C_(2n-1) of odd harmonics ofthe AC magnetization signal, the number of odd harmonics n≧1; and

(5) calculating in-vivo temperature T according to a relationshipbetween the odd harmonics and the in-vivo temperature X=AY, where

the amplitudes of the odd harmonics form a column vector

${X = \begin{bmatrix}C_{1} \\C_{3} \\\vdots \\C_{{2\; n} - 1}\end{bmatrix}};$

a coefficient matrix A is defined as: the AC magnetization signal isexpressed via the Langevin's function, and expression of the amplitudesof the odd harmonics is deduced from a Taylor series expansion of theLangevin's function, and thus the coefficient matrix

${A = \begin{bmatrix}\frac{M_{s}^{2}H_{0}}{a_{1,1}k} & \frac{M_{s}^{4}H_{0}^{3}}{a_{1,2}k^{3}} & \frac{M_{s}^{6}H_{0}^{5}}{a_{1,3}k^{5}} & \ldots & \frac{M_{s}^{2\; m}H_{0}^{{2\; m} - 1}}{a_{1,m}k^{{2\; m} - 1}} \\0 & \frac{M_{s}^{4}H_{0}^{3}}{a_{2,2}k^{3}} & \frac{M_{s}^{6}H_{0}^{5}}{a_{2,3}k^{5}} & \ldots & \frac{M_{s}^{2\; m}H_{0}^{{2\; m} - 1}}{a_{2,m}k^{{2\; m} - 1}} \\\vdots & \ddots & \ddots & \ddots & \vdots \\\vdots & (0) & \ddots & \ddots & \frac{M_{s}^{2\; m}H_{0}^{{2\; m} - 1}}{a_{{n - 1},m}k^{{2\; m} - 1}} \\0 & \ldots & \ldots & \ddots & \frac{M_{s}^{2\; m}H_{0}^{{2\; m} - 1}}{a_{n,m}k^{{2\; m} - 1}}\end{bmatrix}},$where M_(s) is effective magnetic moment of a magnetic nanoparticle, kis a Boltzmann's constant, H₀ is an amplitude of the AC excitationmagnetic field, a_(u,v) is a coefficient of an element at the uth rowand the vth column of the coefficient matrix A, u=1, 2, . . . , n, v=1,2 . . . , m, m is the number of Taylor's expansion terms, and m≧n;

a related column vector Y of the in-vivo temperature is expressed as

${Y = \begin{bmatrix}\frac{N}{T} \\\frac{N}{T^{3}} \\\vdots \\\frac{N}{T^{{2\; m} - 1}}\end{bmatrix}},$where T is the in-vivo temperature of the measured object, and N ismagnetic nano concentration at the measured object.

Advantageously, as the number of the Taylor's expansion terms m is equalto the number of the odd harmonics n, step (5) comprises: calculatingthe related column vector of the in-vivo temperature Y=A⁻¹x, and furtherthe in-vivo temperature T=^(2(q-p))√{square root over (Y_(p)/Y_(q))},1≦p<q≦2n−1, where Y_(p) and Y_(q) respectively represents the p^(th) andthe q^(th) element of the related column vector Y of the in-vivotemperature; and as the number of the Taylor's expansion terms m isgreater than the number of the odd harmonics n, step (5) comprises:performing least square fitting via B=[N,T]^(T) as a variable and therelationship between the odd harmonics and the in-vivo temperature X=AYas an objective function whereby determining the in-vivo temperature T.

Advantageously, step (4) uses a digital phase-sensitive detection methodto detect the amplitudes of the odd harmonics, and comprises sub-stepsof:

(a) sampling the AC magnetization signal M of the magnetic nano agent toobtain a discrete intensity signal M (i), where i=1, 2 . . . , L, and Lis the number of sampling points;

(b) setting j=1;

(c) calculating f′=(2j−1)f, where f is a frequency of the AC excitationmagnetic field;

(d) generating two orthogonal reference signals, and sampling theorthogonal reference signals to obtain two discrete sampling signalsR₁(i) and R₂(i);

(e) determining whether j is equal to 1, proceeding to step (g) if yes,and proceeding to step (f) otherwise;

(f) filtering the 2j−3^(th) odd harmonic in the discrete intensitysignal M(i);

(g) performing mutual correlation calculation and mean filtering on thediscrete sampling signal R₁(i) and the discrete intensity signal M(i) toobtain a first component S_(2j-1), performing mutual correlationcalculation and mean filtering on the discrete sampling signal R₂(i) andthe discrete intensity signal M(i) to obtain a second componentO_(2j-1), and calculating an amplitude of a 2j−1^(th) odd harmonicC_(2j-1)=2√{square root over (S_(2j-1) ²+O_(2j-1) ²)}; and

(h) determining whether j is less than n, setting j=j+1 and retuningstep (c) if yes, and ending otherwise.

Advantageously, step (4) uses a least square system parameteridentification method to detect the amplitudes of the odd harmonics, andcomprises sub-steps of:

sampling the AC magnetization signal M of the magnetic nano agent toobtain a discrete intensity signal M(i), where i=1, 2 . . . , L, and Lis the number of sampling points;

assuming

${Z = {{\begin{bmatrix}{M(1)} \\{M(2)} \\\vdots \\{M(L)}\end{bmatrix}\mspace{14mu}{and}\mspace{14mu}\varphi} = \begin{bmatrix}{\sin(\Omega)} & {\sin( {3\Omega} )} & \ldots & {\sin( {( {{2\; n} - 1} )\Omega} )} \\{\sin( {2\Omega} )} & {\sin( {6\Omega} )} & \ldots & {\sin( {2( {{2\; n} - 1} )\Omega} )} \\\vdots & \vdots & \ddots & \vdots \\{\sin( {L\;\Omega} )} & {\sin( {3\; L\;\Omega} )} & \ldots & {\sin( {{L( {{2\; n} - 1} )}\Omega} )}\end{bmatrix}}},$finding matrices φ and Z so that J=[Z−φX]^(T)[Z−φX] is the minimum byadjusting a sampling frequency, and determining the column vectorX=(φ^(T)φ)⁻¹φ^(T)Z formed by the amplitudes C_(j) of the odd harmonics,where a digital angular frequency

${\Omega = \frac{2\pi\; f}{f_{s}}},$f_(s) represents a sampling frequency, π represents a circumferenceratio, and a superscript T represents transpose.

Advantageously, intensity of the AC excitation magnetic field rangesfrom 20 Oe to 1000 Oe, and a frequency of the AC excitation magneticfield ranges from 20 Hz to 20 kHz.

Advantageously, the number of the odd harmonics ranges from 2 to 4, andthat of the Taylor's expansion terms m ranges from 2 to 6.

It is another objective of the invention to provide a method for in-vivotemperature measurement based on AC magnetization of magneticnanoparticles that is capable of accurately measuring in-vivotemperature without obtaining concentration of the magneticnanoparticles.

An in-vivo temperature measurement system, comprising:

a first module configured to position magnetic nano agent at an area ofa measured object;

a second module configured to apply an AC excitation magnetic field tothe area of the magnetic nano agent;

a third module configured to collect an AC magnetization signal of themagnetic nano agent under the AC excitation magnetic field;

a fourth module configured to detect amplitudes C₁, C₃, . . . , C_(2n-1)of odd harmonics of the AC magnetization signal, the number of oddharmonics n 1; and

a fifth module configured to calculate in-vivo temperature T accordingto a relationship between the odd harmonics and the in-vivo temperatureX=AY, where

the amplitudes of the odd harmonics form a column vector

${X = \begin{bmatrix}C_{1} \\C_{3} \\\vdots \\C_{{2\; n} - 1}\end{bmatrix}};$

a coefficient matrix A is defined as: the AC magnetization signal isexpressed via the Langevin's function, and expression of the amplitudesof the odd harmonics is deduced from a Taylor series expansion of theLangevin's function, and thus the coefficient matrix

${A = \begin{bmatrix}\frac{M_{s}^{2}H_{0}}{a_{1,1}k} & \frac{M_{s}^{4}H_{0}^{3}}{a_{1,2}k^{3}} & \frac{M_{s}^{6}H_{0}^{5}}{a_{1,3}k^{5}} & \ldots & \frac{M_{s}^{2\; m}H_{0}^{{2\; m} - 1}}{a_{1,m}k^{{2\; m} - 1}} \\0 & \frac{M_{s}^{4}H_{0}^{3}}{a_{2,2}k^{3}} & \frac{M_{s}^{6}H_{0}^{5}}{a_{2,3}k^{5}} & \ldots & \frac{M_{s}^{2\; m}H_{0}^{{2\; m} - 1}}{a_{2,m}k^{{2\; m} - 1}} \\\vdots & \ddots & \ddots & \ddots & \vdots \\\vdots & (0) & \ddots & \ddots & \frac{M_{s}^{2\; m}H_{0}^{{2\; m} - 1}}{a_{{n - 1},m}k^{{2\; m} - 1}} \\0 & \ldots & \ldots & \ddots & \frac{M_{s}^{2\; m}H_{0}^{{2\; m} - 1}}{a_{n,m}k^{{2\; m} - 1}}\end{bmatrix}},$where M_(s) is effective magnetic moment of a magnetic nanoparticle, kis a Boltzmann's constant, H₀ is an amplitude of the AC excitationmagnetic field, a_(u,v) is a coefficient of an element at the uth rowand the vth column of the coefficient matrix A, u=1, 2, . . . , n, v=1,2 . . . , m, m is the number of Taylor's expansion terms, and m≧n;

a related column vector Y of the in-vivo temperature is expressed as

${Y = \begin{bmatrix}\frac{N}{T} \\\frac{N}{T^{3}} \\\vdots \\\frac{N}{T^{{2\; m} - 1}}\end{bmatrix}},$where T is the in-vivo temperature of the measured object, and N ismagnetic nano concentration at the measured object.

Advantageously, the fifth module comprises:

a fifty-first sub-module configured to calculate the related columnvector of the in-vivo temperature Y=A⁻¹ X, and further the in-vivotemperature T=^(2(q-p))√{square root over (Y_(p)/Y_(q))}, 1≦p<q≦2n−1 asthe number of the Taylor's expansion terms m is equal to the number ofthe odd harmonics n, where Y_(p) and Y_(q) respectively represents thep^(th) and the q^(th) element of the related column vector Y of thein-vivo temperature; and

a fifty-second sub-module configured to perform least square fitting viaB=[N,T]^(T) as a variable and the relationship between the odd harmonicsand the in-vivo temperature X=AY as an objective function wherebydetermining the in-vivo temperature T as the number of the Taylor'sexpansion terms m is greater than the number of the odd harmonics n.

Advantageously, the fourth module uses a digital phase-sensitivedetection method to detect the amplitudes of the odd harmonics, andcomprises:

a forty-first sub-module configured to sample the AC magnetizationsignal M of the magnetic nano agent to obtain a discrete intensitysignal M(i), where i=1, 2 . . . , L, and L is the number of samplingpoints;

a forty-second sub-module configured to set j=1;

a forty-third sub-module configured to calculate f′=(2j−1)f, where f isa frequency of the AC excitation magnetic field;

a forty-fourth sub-module configured to generate two orthogonalreference signals, and to sample the orthogonal reference signals toobtain two discrete sampling signals R₁(i) and R₂(i);

a forty-fifth sub-module configured to determine whether j is equal to1, to proceed to step (g) if yes, and to proceed to step (f) otherwise;

a forty-sixth sub-module configured to filter the 2j−3^(th) odd harmonicin the discrete intensity signal M(i);

a forty-seventh sub-module configured to perform mutual correlationcalculation and mean filtering on the discrete sampling signal R₁(i) andthe discrete intensity signal M (i) to obtain a first componentS_(2j-1), to perform mutual correlation calculation and mean filteringon the discrete sampling signal R₂(i) and the discrete intensity signalM (i) to obtain a second component O_(2j-1), and to calculate anamplitude of a 2j−1^(th) odd harmonic C_(2j-1)=2√{square root over(S_(2j-1) ²+O_(2j-1) ²)}; and

a forty-eighth sub-module configured to determine whether j is less thann, to set j=j+1 and return step (c) if yes, and to end otherwise.

Advantageously, the fourth module uses a least square system parameteridentification method to detect the amplitudes of the odd harmonics,

the fourth module is configured to sample the AC magnetization signal Mof the magnetic nano agent to obtain a discrete intensity signal M(i),where i=1, 2 . . . , L, and L is the number of sampling points;

assuming

${Z = {{\begin{bmatrix}{M(1)} \\{M(2)} \\\vdots \\{M(L)}\end{bmatrix}\mspace{14mu}{and}\mspace{14mu}\varphi} = \begin{bmatrix}{\sin(\Omega)} & {\sin( {3\Omega} )} & \ldots & {\sin( {( {{2\; n} - 1} )\Omega} )} \\{\sin( {2\Omega} )} & {\sin( {6\Omega} )} & \ldots & {\sin( {2( {{2\; n} - 1} )\Omega} )} \\\vdots & \vdots & \ddots & \vdots \\{\sin( {L\;\Omega} )} & {\sin( {3\; L\;\Omega} )} & \ldots & {\sin( {{L( {{2\; n} - 1} )}\Omega} )}\end{bmatrix}}},$to find matrices φ and Z so that J=[Z−φX]^(T)[Z−φX] is the minimum byadjusting a sampling frequency, and to determine the column vectorX=(φ^(T)φ)⁻¹φ^(T)Z formed by the amplitudes C_(j) of the odd harmonics,where a digital angular frequency

${\Omega = \frac{2\pi\; f}{f_{s}}},$f_(s) represents a sampling frequency, π represents a circumferenceratio, and a superscript T represents transpose.

Advantages of the Invention Comprise:

The invention applies the AC excitation magnetic field to the field ofthe magnetic nano agent, collects the AC magnetization of the magneticnano agent under the AC excitation magnetic field, detects the oddharmonics of the AC magnetization signal of the magnetic nanoparticles,analyzes spectrum information of a magnetic intensity model of themagnetic nanoparticles via the discrete Langevin's function and theFourier transformation, establishes a matrix relationship between theodd harmonics and temperature and concentration of the magneticnanoparticles, and solves the in-vivo temperature according to therelationship without considering concentration of the magneticnanoparticles, and effective moment as temperature varies, and thusaccurately detecting the in-vivo temperature. In addition, the inventionis capable of accurately and rapidly detecting the in-vivo temperature,and is especially applicable to detect thermal motion of biologicalmolecules, and an average error thereof after ten times of measurementexperiments at a SNR of 80 dB is less than 0.2K.

DESCRIPTION OF ACCOMPANYING DRAWINGS

FIG. 1 is a flowchart of a method for in-vivo temperature measurement ofan exemplary embodiment of the invention;

FIG. 2 illustrates principle of a digital phase-sensitive detection(DPSD) method;

FIG. 3 illustrates measurement of different harmonics using the digitalphase-sensitive detection method;

FIG. 4 illustrates measurement of different harmonics using a leastsquare system parameter identification method;

FIG. 5 illustrates temperature estimation errors obtained by measuringharmonics via the DPSD and the least square system parameteridentification method at an excitation frequency of 1 kH;

FIG. 6 illustrates temperature estimation errors obtained by measuringharmonics via the DPSD and the least square system parameteridentification method at an excitation frequency of 5 kH; and

FIG. 7 illustrates temperature estimation errors obtained by measuringharmonics via the DPSD and the least square system parameteridentification method at an excitation frequency of 10 kH.

SPECIFIC EMBODIMENT OF THE INVENTION

For clear understanding of the objectives, features and advantages ofthe invention, detailed description of the invention will be given belowin conjunction with accompanying drawings and specific embodiments. Itshould be noted that the embodiments are only meant to explain theinvention, and not to limit the scope of the invention.

As shown in FIG. 1, a method for in-vivo temperature measurement of theinvention comprises steps of:

(1) positioning magnetic nano agent at an area of a measured object;

in details, firstly surface of magnetic nanoparticles is covered withmodification agent, and then the magnetic nanoparticles are redirectedto the measured objects, such as various biological organs, along withblood circulation systems via injection.

(2) applying an AC excitation magnetic field to the area of the magneticnano agent;

Using a Taylor series expansion of the Langevin's function ofmagnetization to calculate amplitudes of odd harmonics in the followingsteps is based on a weak excitation magnetic field, but a too weakexcitation magnetic field is to lead to a small SNR of themagnetization, and make it difficult to extract high harmonics.Therefore, it is very important to select an appropriate strength forthe AC excitation magnetic field, normally 20˜1000 Oe, andadvantageously 100 Oe. In addition, a frequency of the AC excitationmagnetic field is 20 Hz to 20 kHz, and advantageously 1 kHz.

(3) collecting an AC magnetization signal of the magnetic nano agentunder the AC excitation magnetic field;

a detection coil as a sensor is placed in the vicinity of the measuredobject containing the magnetic nano agent, magnetization analog signalinduced thereby is pre-processed by a conditioning circuit, and thensampled and transmitted to a computer for further procession via a dataacquisition card.

(4) detecting amplitudes of odd harmonics of the AC magnetizationsignal;

firstly, the AC magnetization signal is modeled: AC magnetization ofmagnetic nanoparticles with paramagnetic characteristics follows theLangevin's function as follows:

$M = {{{NM}_{s}\lbrack {{\coth( \frac{M_{s}H}{kT} )} - \frac{kT}{M_{s}H}} \rbrack} = {{NM}_{s}{L( \frac{M_{s}H}{kT} )}}}$

where

$L( \frac{M_{s}H}{kT} )$is the Langevin's function, N is concentration of the magnetic nanoagent, the excitation magnetic field H=H₀ sin (2π ft), H₀ is a amplitudeof the excitation magnetic field, f is a frequency of the excitationmagnetic field, M_(s) is effective magnetic moment of the magneticnanoparticle, k is the Boltzmann's constant, T is temperature of themagnetic nanoparticle, namely in-vivo temperature of the measuredobject.

Then the above equation is divided into multiple frequency mixingsignals containing multiple odd harmonics, namely

${M = {\sum\limits_{j = 1}^{n}\;{C_{{2\; j} - 1}{\sin( {{2\; j} - 1} )}\omega\; t}}},{n \geq 1}$

where C_(2j-1) is an amplitude of the 2j−1^(th) odd harmonic, an angularfrequency ω=2πf, t is time, n is the preset number of polynominalexpansion terms that determines the number of all measured oddharmonics, if n is too small, an approximation error of finite terms ofthe AC magnetization and thus a temperature estimation error becomelarge, if n is too large, it is difficult to accurately detect weakamplitude signals of high harmonics, and thus the temperature estimationerror is to be increased. It is suggested that n range from 2 to 4.

By replacing the Fourier equation

$C_{{2\; j} - 1} = {\frac{1}{\pi}{\int_{- \pi}^{\pi}{M\;{\sin( {( {{2\; j} - 1} )\omega\; t} )}\ {\mathbb{d}\omega}\; t}}}$with the Taylor series expansions

${M = {{\frac{{NM}_{s}^{2}}{3\;{kT}}H} - {\frac{{NM}_{s}^{4}}{45\; k^{3}T^{3}}H^{3}} + {\frac{2\;{NM}_{s}^{6}}{945\; k^{5}T^{5}}H^{5}} - {\frac{{NM}_{s}^{8}}{4725\; k^{7}T^{7}}H^{7}\mspace{14mu}\ldots} + {\frac{{NM}_{s}^{2\; m}}{b_{m}\; k^{{2\; m} - 1}T^{{2\; m} - 1}}H^{{2\; m} - 1}}}},$

it is possible to obtain an expression for an amplitude C_(2j-1) of eachharmonic, b_(m) is a constant, the number of Taylor's expansion terms mranges from 2 to 6, and m≧n

An example in which the number of odd harmonics n=4 and the number ofTaylor's expansion terms m=4 will be given below:

${M = {{C_{1}{\sin( {\omega\; t} )}} + {C_{3}{\sin( {3\omega\; t} )}} + {C_{5}{\sin( {5\omega\; t} )}} + {C_{7}{\sin( {7\omega\; t} )}}}},{{where}\{ {\begin{matrix}{C_{1} = {\frac{{NM}_{s}^{2}H_{0}}{3\;{kT}} - \frac{{NM}_{s}^{4}H_{0}^{3}}{60\; k^{3}T^{3}} + \frac{{NM}_{s}^{6}H_{0}^{5}}{756\; k^{5}T^{5}} - \frac{{NM}_{s}^{8}H_{0}^{7}}{8640\; k^{7}T^{7}}}} \\{C_{3} = {\frac{{NM}_{s}^{4}H_{0}^{3}}{180\; k^{3}T^{3}} - \frac{{NM}_{s}^{6}H_{0}^{5}}{1512\; k^{5}T^{5}} + \frac{{NM}_{s}^{8}H_{0}^{7}}{14400\; k^{7}T^{7}}}} \\{C_{5} = {\frac{{NM}_{s}^{6}H_{0}^{5}}{7560\; k^{5}T^{5}} - \frac{{NM}_{s}^{8}H_{0}^{7}}{43200\; k^{7}T^{7}}}} \\{C_{7} = \frac{{NM}_{s}^{8}H_{0}^{7}}{302400\; k^{7}T^{7}}}\end{matrix},} }$

the odd harmonics are proportional to concentration of the particles perunit volume, and harmonic ratios are functionally related to temperatureand irrelevant to the concentration, and can prove approximation of thetemperature without knowing particle concentration.

Based on the above model, this step employs a digital phase-sensitivedetection (DPSD) method and a least square system parameteridentification method to measure the amplitudes of the odd harmonics ofdifferent AC magnetization.

Measurement of an amplitude of a fundamental harmonic C₁, an amplitudeof a third harmonic C₃, an amplitude of a fifth harmonic C₅, and anamplitude of a seventh harmonic C₇ of different AC magnetization usingthe DPSD and the least square system parameter identification method isdescribed below with reference to an example in which the number of theharmonics n=4.

A. Using the DPSD to Measure the Amplitudes of the Odd Harmonics

FIG. 2 illustrates a principle of the DPSD. Firstly two orthogonalreference signals are set according to a particular frequency to beextracted f′: R₁(t)=cos(2πf′t), R₂(t)=sin(2πf′t), and then respectivelymutually correlated with a measured signal M(t), then mean-filteredwhereby forming two components

${S = {{\frac{A}{2}\sin\;\theta\mspace{14mu}{and}\mspace{14mu} O} = {\frac{A}{2}\cos\;\theta}}},$where A is a amplitude of the particular frequency, θ is a phase angleof the particular frequency, and finally the amplitude and the phaseangle can be obtained according to equations A=2√{square root over(S²+O²)} and

$\theta = {\arctan{\frac{S}{O}.}}$

FIG. 3 illustrates measurement of different harmonics using the digitalphase-sensitive detection method, and a detailed measurement process isas follows:

A1. Signal Sampling

The AC magnetization signal M of the magnetic nanoparticles is M(i)=C₁sin (Ωi)+C₃ sin (3 Ωi)+C₅ sin (5 Ωi)+C₇ sin (7 Ωi)+ε(i) afteranalog-digital conversion, and the two reference signals areR₁(i)=cos(Ω′i), R₂(i)=sin(Ω′i) after analog-digital conversion, where fis an excitation frequency, f_(s) is a sampling frequency, a digitalangular frequency

${\Omega = \frac{2\pi\; f}{f_{s}}},\mspace{14mu}{\Omega^{\prime} = \frac{2\pi\; f^{\prime}}{f_{s}}},$sampling points i=1, 2 . . . , L, L is the length of discrete samplingseries, ε(.) is an error function containing high harmonics.

A2. Extraction of Amplitudes of Harmonics

(1) To obtain an amplitude of the fundamental harmonic, assume f′=f anduse the DPSD method to get:

$S_{1} = {{\frac{1}{L}{\sum\limits_{i = 1}^{L}\;{{M(i)}{R_{1}(i)}}}} = {\frac{C_{1}}{2}\sin\;\theta}}$$O_{1} = {{\frac{1}{L}{\sum\limits_{i = 1}^{L}\;{{M(i)}{R_{2}(i)}}}} = {\frac{C_{1}}{2}\cos\;\theta}}$

then the amplitude of the fundamental harmonic isC ₁=2√{square root over (S ₁ ² +O ₁ ²)}(2) after the amplitude C₁ of the fundamental harmonic is obtained, toobtain the amplitude C₃ of the third harmonic with high accuracy, assumef′=3 f and use the DPSD method to process a magnetization signal M′after filtering the fundamental harmonic and get:

$S_{3} = {{\frac{1}{L}{\sum\limits_{i = 1}^{L}\;{{M^{\prime}(i)}{R_{1}(i)}}}} = {\frac{C_{3}}{2}\sin\;\theta}}$$O_{3} = {{\frac{1}{L}{\sum\limits_{i = 1}^{L}\;{{M^{\prime}(i)}{R_{2}(i)}}}} = {\frac{C_{3}}{2}\cos\;\theta}}$

then the amplitude of the third harmonic isC ₃=2√{square root over (S ₃ ² +O ₃ ²)}(3) after the amplitude C₃ of the third harmonic is obtained, for themagnetization M″ after the third harmonic of M′ is filtered, assumef′=5f and use the DPSD method to get:

$S_{5} = {{\frac{1}{L}{\sum\limits_{i = 1}^{L}\;{{M^{''}(i)}{R_{1}(i)}}}} = {\frac{C_{5}}{2}\sin\;\theta}}$$O_{5} = {{\frac{1}{L}{\sum\limits_{i = 1}^{L}\;{{M^{''}(i)}{R_{2}(i)}}}} = {\frac{C_{5}}{2}\cos\;\theta}}$

then the amplitude of the fifth harmonic isC ₅=2√{square root over (S ₅ ² +O ₅ ²)}(4) after the amplitude C₅ of the fifth harmonic is obtained, for themagnetization M′″ after the third harmonic of M″ is filtered, assumef′=7 f and use the DPSD method to get:

$S_{7} = {{\frac{1}{L}{\sum\limits_{i = 1}^{L}\;{{{M^{\prime}}^{''}(i)}{R_{1}(i)}}}} = {\frac{C_{7}}{2}\sin\;\theta}}$$O_{7} = {{\frac{1}{L}{\sum\limits_{i = 1}^{L}\;{{{M^{\prime}}^{''}(i)}{R_{2}(i)}}}} = {\frac{C_{7}}{2}\cos\;\theta}}$

then the amplitude of the seventh harmonic isC ₇=2√{square root over (S ₇ ² +O ₇ ²)}

By performing the above steps, it is possible to extract the amplitudesof the harmonics in the AC magnetization signal of the magneticnanoparticles via the DPSD method.

B. Using the Least Square System Parameter Identification Method toMeasure Harmonics

FIG. 4 illustrates measurement of different harmonics using the leastsquare system parameter identification method, and a detailedmeasurement process is as follows:

Signal sampling: The AC magnetization signal M of the magneticnanoparticles is M(i)=C₁ sin (Ωi)+C₃ sin (3 Ωi)+C₅ sin (5 Ωi)+C₇ sin (7Ωi)+ε(i) after analog-digital conversion, where f is an excitationfrequency, f_(s) is a sampling frequency, a digital angular frequency

${\Omega = \frac{2\pi\; f}{f_{s}}},$sampling points i=1, 2 . . . , L, ε(.) is an error function containinghigh harmonics, and L is the length of discrete sampling series.

Then the above equation is further converted to a matrix relationship:

${\begin{bmatrix}{M(1)} \\{M(2)} \\\vdots \\{M(L)}\end{bmatrix} = {{\begin{bmatrix}{\sin(\Omega)} & {\sin( {3\Omega} )} & {\sin( {5\Omega} )} & {\sin( {7\Omega} )} \\{\sin( {2\Omega} )} & {\sin( {6\Omega} )} & {\sin( {10\Omega} )} & {\sin( {14\Omega} )} \\\vdots & \vdots & \vdots & \vdots \\{\sin( {L\;\Omega} )} & {\sin( {3\; L\;\Omega} )} & {\sin( {5\; L\;\Omega} )} & {\sin( {7\; L\;\Omega} )}\end{bmatrix}\begin{bmatrix}C_{1} \\C_{3} \\C_{5} \\C_{7}\end{bmatrix}} + \begin{bmatrix}{ɛ(1)} \\{ɛ(2)} \\\vdots \\{ɛ(L)}\end{bmatrix}}},{{{assume}\mspace{14mu} Z} = \begin{bmatrix}{M(1)} \\{M(2)} \\\vdots \\{M(L)}\end{bmatrix}},{\varphi = \begin{bmatrix}{\sin(\Omega)} & {\sin( {3\Omega} )} & {\sin( {5\Omega} )} & {\sin( {7\Omega} )} \\{\sin( {2\Omega} )} & {\sin( {6\Omega} )} & {\sin( {10\Omega} )} & {\sin( {14\Omega} )} \\\vdots & \vdots & \vdots & \vdots \\{\sin( {L\;\Omega} )} & {\sin( {3\; L\;\Omega} )} & {\sin( {5\; L\;\Omega} )} & {\sin( {7\; L\;\Omega} )}\end{bmatrix}},{X = \begin{bmatrix}C_{1} \\C_{3} \\C_{5} \\C_{7}\end{bmatrix}},{e = \begin{bmatrix}{ɛ(1)} \\{ɛ(2)} \\\vdots \\{ɛ(L)}\end{bmatrix}},{{{then}\mspace{14mu} Z} = {{\varphi\; X} + e}},{{{an}\mspace{14mu}{error}\mspace{14mu}{vector}\mspace{14mu} e} = {Z - {\varphi\;{X.}}}}$

In the model, the least square system parameter identification methodassesses fitting of measurement data based on estimation of a unknownparameter vector X being capable of minimizing square sum of errors,namely

$J = {{\sum\limits_{i = 1}^{L}\;{ɛ^{2}(i)}} = {{\mathbb{e}}^{T}{e.}}}$To minimize J=[Z−φX]^(T)[Z−φX], it is required to find appropriatematrices φ and Z by adjusting a sampling frequency. Assume an optimumestimation column vector {circumflex over (X)}=(φ^(T)φ)⁻¹φ^(T)Z, let

${ \frac{\partial J}{\partial\hat{X}} |_{X = X} = 0},$namely J is the minimum. Thus, the amplitude of the fundamental harmonicC₁, the amplitude of the third harmonic C₃, the amplitude of the fifthharmonic C₅, and the amplitude of the seventh harmonic C₇ can beobtained from the optimum estimation column vector {circumflex over(X)}.

(5) calculating in-vivo temperature according to the matrix relationshipbetween the amplitudes C_(2j-1) of the odd harmonics and the in-vivotemperature T;

The amplitudes C_(2j-1) of the odd harmonics and the in-vivo temperatureT follow a matrix relationship X=AY, where

X is a column vector formed by the amplitudes C_(2j-1) of the oddharmonics, and

${X = \begin{bmatrix}C_{1} \\C_{3} \\\vdots \\C_{{2\; n} - 1}\end{bmatrix}},$

Y is a related column vector of the in-vivo temperature, and

${Y = \begin{bmatrix}\frac{N}{T} \\\frac{N}{T^{3}} \\\vdots \\\frac{N}{T^{{2\; m} - 1}}\end{bmatrix}},$

the coefficient matrix A is defined as: the AC magnetization signal isexpressed via the Langevin's function, and expression of the amplitudesof the odd harmonics is deduced from a Taylor series expansion of theLangevin's function, and thus the coefficient matrix

${A = \begin{bmatrix}\frac{M_{s}^{2}H_{0}}{a_{1,1}k} & \frac{M_{s}^{4}H_{0}^{3}}{a_{1,2}k^{3}} & \frac{M_{s}^{6}H_{0}^{5}}{a_{1,3}k^{5}} & \ldots & \frac{M_{s}^{2\; m}H_{0}^{{2\; m} - 1}}{a_{1,m}k^{{2\; m} - 1}} \\0 & \frac{M_{s}^{4}H_{0}^{3}}{a_{2,2}k^{3}} & \frac{M_{s}^{6}H_{0}^{5}}{a_{2,3}k^{5}} & \ldots & \frac{M_{s}^{2\; m}H_{0}^{{2\; m} - 1}}{a_{2,m}k^{{2\; m} - 1}} \\\vdots & \ddots & \ddots & \ddots & \vdots \\\vdots & (0) & \ddots & \ddots & \frac{M_{s}^{2\; m}H_{0}^{{2\; m} - 1}}{a_{{n - 1},m}k^{{2\; m} - 1}} \\0 & \ldots & \ldots & \ddots & \frac{M_{s}^{2\; m}H_{0}^{{2\; m} - 1}}{a_{n,m}k^{{2\; m} - 1}}\end{bmatrix}},$where a_(u,v) is a coefficient of an element at the uth row and the vthcolumn of the coefficient matrix A, u=1, 2, . . . , n, v=1, 2 . . . , m,m≧n.

Using the above relationship between the harmonics and the temperatureX=AY to solve the in-vivo temperature comprises the following twoscenarios:

(a) as the number of the Taylor's expansion terms m is equal to thenumber of the odd harmonics n, step (5) comprises: calculating therelated column vector of the in-vivo temperature Y=A⁻¹ X, and furtherthe in-vivo temperature T=^(2(q-p))√{square root over (Y_(p)/Y_(q))},1≦p<q≦2n−1, where Y_(p) and Y_(q) respectively represents the p^(th) andthe q^(th) element of the related column vector Y of the in-vivotemperature;

(b) as the number of the Taylor's expansion terms m is greater than thenumber of the odd harmonics n, step (5) comprises: performing leastsquare fitting via B=[N,T]^(T) as a variable and the relationshipbetween the odd harmonics and the in-vivo temperature X=AY as anobjective function whereby determining the in-vivo temperature T.

An example in which m=n=4 is described as follows:

$\quad\{ \begin{matrix}{C_{1} = {\frac{{NM}_{s}^{2}H_{0}}{3\;{kT}} - \frac{{NM}_{s}^{4}H_{0}^{3}}{60\; k^{3}T^{3}} + \frac{{NM}_{s}^{6}H_{0}^{5}}{756\; k^{5}T^{5}} - \frac{{NM}_{s}^{8}H_{0}^{7}}{8640\; k^{7}T^{7}}}} \\{C_{3} = {\frac{{NM}_{s}^{4}H_{0}^{3}}{180\; k^{3}T^{3}} - \frac{{NM}_{s}^{6}H_{0}^{5}}{1512\; k^{5}T^{5}} + \frac{{NM}_{s}^{8}H_{0}^{7}}{14400\; k^{7}T^{7}}}} \\{C_{5} = {\frac{{NM}_{s}^{6}H_{0}^{5}}{7560\; k^{5}T^{5}} - \frac{{NM}_{s}^{8}H_{0}^{7}}{43200\; k^{7}T^{7}}}} \\{C_{7} = \frac{{NM}_{s}^{8}H_{0}^{7}}{302400\; k^{7}T^{7}}}\end{matrix} $is converted to a matrix relationship:

${\begin{bmatrix}C_{1} \\C_{3} \\C_{5} \\C_{7}\end{bmatrix} = {\begin{bmatrix}\frac{M_{s}^{2}H_{0}}{3k} & {- \frac{M_{s}^{4}H_{0}^{3}}{60k^{3}}} & \frac{M_{s}^{6}H_{0}^{5}}{756k^{5}} & {- \frac{M_{s}^{8}H_{0}^{7}}{8640k^{7}}} \\0 & \frac{M_{s}^{4}H_{0}^{3}}{180k^{3}} & {- \frac{M_{s}^{6}H_{0}^{5}}{1512k^{5}}} & \frac{M_{s}^{8}H_{0}^{7}}{14400k^{7}} \\0 & 0 & \frac{M_{s}^{6}H_{0}^{5}}{7560k^{5}} & {- \frac{M_{s}^{8}H_{0}^{7}}{43200k^{7}}} \\0 & 0 & 0 & \frac{M_{s}^{8}H_{0}^{7}}{302400k^{7}}\end{bmatrix}\begin{bmatrix}\frac{N}{T} \\\frac{N}{T^{3}} \\\frac{N}{T^{5}} \\\frac{N}{T^{7}}\end{bmatrix}}},$assume a related column vector of the temperature

${{T\text{:}\mspace{14mu} Y} = \begin{bmatrix}\frac{N}{T} \\\frac{N}{T^{3}} \\\frac{N}{T^{5}} \\\frac{N}{T^{7}}\end{bmatrix}},$the amplitudes of the odd harmonics form a column vector

${X = \begin{bmatrix}C_{1} \\C_{3} \\C_{5} \\C_{7}\end{bmatrix}},$coefficient matrix A is

$\quad\begin{bmatrix}\frac{M_{s}^{2}H_{0}}{3k} & {- \frac{M_{s}^{4}H_{0}^{3}}{60k^{3}}} & \frac{M_{s}^{6}H_{0}^{5}}{756k^{5}} & {- \frac{M_{s}^{8}H_{0}^{7}}{8640k^{7}}} \\0 & \frac{M_{s}^{4}H_{0}^{3}}{180k^{3}} & {- \frac{M_{s}^{6}H_{0}^{5}}{1512k^{5}}} & \frac{M_{s}^{8}H_{0}^{7}}{14400k^{7}} \\0 & 0 & \frac{M_{s}^{6}H_{0}^{5}}{7560k^{5}} & {- \frac{M_{s}^{8}H_{0}^{7}}{43200k^{7}}} \\0 & 0 & 0 & \frac{M_{s}^{8}H_{0}^{7}}{302400k^{7}}\end{bmatrix}$

then the related column vector of the in-vivo temperature is calculatedY=A⁻¹ X, thus the temperature T can be measured by any two dimensionaldata (such as the p^(th) dimension and the q^(th) dimension) withoutknowing concentration of the magnetic nanoparticles, namely

${T = {\sqrt[{2( {q - p} )}]{Y_{p}/Y_{q}} = \sqrt[{2( {q - p} )}]{( \frac{N}{T^{{2p} - 1}} )/( \frac{N}{T^{{2q} - 1}} )}}},{1 \leq p < q \leq 4}$

where Y_(p) and Y_(q) respectively represents the p^(th) and the q^(th)element of the related column vector Y of the in-vivo temperature.Advantageously, as P=1, q=2, highly accurate results can be obtained.

Simulation Example 1. Simulation Model and Test Description

To study effectiveness of the temperature measurement method and tooptimize design, the example uses simulation data with noise to test thealgorithm of the invention. During simulation and testing, effectivemoment M_(s) of the particles in the agent is 4×10⁻¹⁹ (the value isdetermined by the type of the agent). Since a quadrinomial approximationmodel of the Fourier series of the AC magnetization causes error effect,an AC excitation magnetic field with a small amplitude must be used. Inthis example, the amplitude of the AC excitation magnetic field H₀=100Oe. A noise model uses a function in the MATLAB software named ‘awgn’ toapply noise with a preset SNR to the AC magnetization of the samplingsignal. A SNR during temperature measurement is set to 80 dB, afrequency of the excitation magnetic field is set to 1 kHz (lowfrequency point), 5 kHz (middle frequency point) and 10 kHz (highfrequency point) for different purposes, and a temperature test range isbetween 300 K to 340 K.

To test accuracy of the temperature measurement method of the invention,the simulation uses the DPSD method and the least square systemparameter identification method to test temperature estimation errorsobtained from different harmonics in the AC magnetization of themagnetic nanoparticles. Meanwhile, to test repeatability of the method,an average temperature estimation error after ten times of repeatedmeasurement is used. FIGS. 5 to 7 respectively illustrates an averagetemperature estimation error obtained by measuring harmonics via theDPSD and the least square system parameter identification method at anlow excitation frequency of 1 kH, a middle excitation frequency of 5kHz, and a high excitation frequency of 10 kHz.

2. Simulation Results

FIGS. 5 to 7 indicate no matter what frequency is used (a low frequencyof 1 kHz, a middle frequency of 5 kHz, or a high frequency of 10 kHz),temperature estimation errors obtained by measuring harmonics via theDPSD and the least square system parameter identification method can becontrolled below 0.2 K, and accuracy, stability and repeatability duringmeasurement can be ensured. As a test SNR is set to 80 dB, thetemperature measurement method of the invention features good noiseresistance performance, and provides a new solution for accurate andfast noninvasive detection of organisms' temperature under highlycomplicated circumstances in the future.

While preferred embodiments of the invention have been described above,the invention is not limited to disclosure in the embodiments and theaccompanying drawings. Any changes or modifications without departingfrom the spirit of the invention fall within the scope of the invention.

What is claimed is:
 1. A method for in-vivo temperature measurement,comprising steps of: (1) positioning a magnetic nano agent at an area ofa measured object; (2) applying an AC excitation magnetic field to saidarea; (3) collecting an AC magnetization signal of said magnetic nanoagent under said AC excitation magnetic field using a coil sensor andprocessing the AC magnetization signal via a data acquisition card; (4)detecting amplitudes C₁, C₃, . . . , C_(2n-1) of odd harmonics of saidAC magnetization signal, a number of said odd harmonics n≧1; and (5)calculating in-vivo temperature T according to equation X=AY, whereinsaid amplitudes of said odd harmonics form a column vector${X = \begin{bmatrix}C_{1} \\C_{3} \\\vdots \\C_{{2n} - 1}\end{bmatrix}};$ wherein a coefficient matrix A is defined by expressingsaid AC magnetization signal via Langevin's function, and deducing anexpression of said amplitudes of said odd harmonics from a Taylor seriesexpansion of the Langevin's function, thereby obtaining said coefficientmatrix $A = {\quad{\begin{bmatrix}\frac{M_{s}^{2}H_{0}}{a_{1,1}k} & \frac{M_{s}^{4}H_{0}^{3}}{a_{1,2}k^{3}} & \frac{M_{s}^{6}H_{0}^{5}}{a_{1,3}k^{5}} & \ldots & \frac{M_{s}^{2m}H_{0}^{{2m} - 1}}{a_{1,m}k^{{2m} - 1}} \\0 & \frac{M_{s}^{4}H_{0}^{3}}{a_{2,2}k^{3}} & \frac{M_{s}^{6}H_{0}^{5}}{a_{2,3}k^{5}} & \ldots & \frac{M_{s}^{2m}H_{0}^{{2m} - 1}}{a_{2,m}k^{{2m} - 1}} \\\vdots & \ddots & \ddots & \ddots & \vdots \\\vdots & (0) & \ddots & \ddots & \frac{M_{s}^{2m}H_{0}^{{2m} - 1}}{a_{{n - 1},m}k^{{2m} - 1}} \\0 & \ldots & \ldots & \ddots & \frac{M_{s}^{2m}H_{0}^{{2m} - 1}}{a_{n,m}k^{{2m} - 1}}\end{bmatrix},}}$  where M_(s) is effective magnetic moment of amagnetic nanoparticle, k is a Boltzmann's constant, H₀ is an amplitudeof said AC excitation magnetic field, a_(u,v) is a coefficient of anelement at the uth row and the vth column of said coefficient matrix A,where u=1, 2, . . . , n, v=1, 2 . . . , m, and m is a number of Taylor'sexpansion terms, and m≧n; wherein a related column vector Y of saidin-vivo temperature is expressed as ${Y = \begin{bmatrix}\frac{N}{T} \\\frac{N}{T^{3}} \\\vdots \\\frac{N}{T^{{2m} - 1}}\end{bmatrix}},$  where T is said in-vivo temperature of said measuredobject, and N is magnetic nano concentration at said measured object. 2.The method for in-vivo temperature measurement of claim 1, wherein whenthe number of said Taylor's expansion terms m is equal to the number ofsaid odd harmonics n, step (5) is performed by calculating said relatedcolumn vector of said in-vivo temperature Y=A⁻¹X, and further saidin-vivo temperature T=^(2(q-p))√{square root over (Y_(p)/Y_(q))},1≦p<q≦2n−1, where Y_(p) and Y_(q) respectively represents the p^(th) andthe q^(th) element of said related column vector Y of said in-vivotemperature; and wherein when the number of said Taylor's expansionterms m is greater than the number of said odd harmonics n, step (5) isperformed by performing least square fitting via B=[N,T]^(T) as avariable and the relationship between said odd harmonics and saidin-vivo temperature X=AY as an objective function whereby determiningsaid in-vivo temperature T.
 3. The method for in-vivo temperaturemeasurement of claim 1, wherein step (4) uses a digital phase-sensitivedetection method to detect said amplitudes of said odd harmonics, andcomprises sub-steps of: (a) sampling said AC magnetization signal M ofsaid magnetic nano agent to obtain a discrete intensity signal M(i),where 1=1, 2 . . . , L, and L is the number of sampling points; (b)setting j=1; (c) calculating f′=(2j−1)f, where f is a frequency of saidAC excitation magnetic field; (d) generating two orthogonal referencesignals, and sampling said orthogonal reference signals to obtain twodiscrete sampling signals R₁(i) and R₂(i); (e) determining whether j isequal to 1, proceeding to step (g) if yes, and proceeding to step (f)otherwise; (f) filtering the 2j−3^(th) odd harmonic in said discreteintensity signal M(i); (g) performing mutual correlation calculation andmean filtering on the discrete sampling signal R₁(i) and said discreteintensity signal M(i) to obtain a first component S_(2j-1), performingmutual correlation calculation and mean filtering on the discretesampling signal R₂(i) and said discrete intensity signal M(i) to obtaina second component O_(2j-1), and calculating an amplitude of a 2j−1^(th)odd harmonic C_(2j-1)=2√{square root over (S_(2j-1) ²+O_(2j-1) ²)}; and(h) determining whether j is less than n, setting j=j+1 and retuningstep (c) if yes, and ending otherwise.
 4. The method for in-vivotemperature measurement of claim 1, wherein step (4) uses a least squaresystem parameter identification method to detect said amplitudes of saidodd harmonics, and comprises sub-steps of: sampling said ACmagnetization signal M of said magnetic nano agent to obtain a discreteintensity signal M(i), where 1=1, 2 . . . , L, and L is the number ofsampling points; ${{assuming}\mspace{14mu} Z} = {\begin{bmatrix}{M(1)} \\{M(2)} \\\vdots \\{M(L)}\end{bmatrix}\mspace{14mu}{and}}$ ${\varphi = \begin{bmatrix}{\sin(\Omega)} & {\sin( {3\Omega} )} & \ldots & {\sin( {( {{2n} - 1} )\Omega} )} \\{\sin( {2\Omega} )} & {\sin( {6\Omega} )} & \ldots & {\sin( {2( {{2n} - 1} )\Omega} )} \\\vdots & \vdots & \ddots & \vdots \\{\sin( {L\;\Omega} )} & {\sin( {3L\;\Omega} )} & \ldots & {\sin( {{L( {{2n} - 1} )}\Omega} )}\end{bmatrix}},$ finding matrices φ and Z so that J=[Z−φX]^(T)[Z−φX] isminimum by adjusting a sampling frequency, and determining said columnvector X=(φ^(T)φ)⁻¹φ^(T)Z formed by said amplitudes C_(j) of said oddharmonics, where a digital angular frequency${\Omega = \frac{2\pi\; f}{f_{s}}},$  f_(s) represents a samplingfrequency, π represents a circumference ratio, and a superscript Trepresents transpose.
 5. The method for in-vivo temperature measurementof claim 1, wherein intensity of said AC excitation magnetic fieldranges from 20 Oe to 1000 Oe, and a frequency of said AC excitationmagnetic field ranges from 20 Hz to 20 kHz.
 6. The method for in-vivotemperature measurement of claim 1, wherein the number of said oddharmonics n ranges from 2 to 4, and the number of said Taylor'sexpansion terms m ranges from 2 to
 6. 7. An in-vivo temperaturemeasurement system, comprising: a first module configured to position amagnetic nano agent at an area of a measured object; a second moduleconfigured to apply an AC excitation magnetic field to said area; athird module configured to collect an AC magnetization signal of saidmagnetic nano agent under said AC excitation magnetic field in a digitalform, the third module comprising a coil sensor and a data acquisitioncard; a fourth module configured to detect amplitudes C₁, C₃, . . . ,C_(2n-1) of odd harmonics of said AC magnetization signal, a number ofsaid odd harmonics n≧1; and a fifth module configured to calculatein-vivo temperature T according to equation X=AY, wherein saidamplitudes of said odd harmonics form a column vector${X = \begin{bmatrix}C_{1} \\C_{3} \\\vdots \\C_{{2n} - 1}\end{bmatrix}};$ wherein a coefficient matrix A is defined by expressingsaid AC magnetization signal via Langevin's function, and deducing anexpression of said amplitudes of said odd harmonics from a Taylor seriesexpansion of the Langevin's function, thereby obtaining said coefficientmatrix $A = {\quad{\begin{bmatrix}\frac{M_{s}^{2}H_{0}}{a_{1,1}k} & \frac{M_{s}^{4}H_{0}^{3}}{a_{1,2}k^{3}} & \frac{M_{s}^{6}H_{0}^{5}}{a_{1,3}k^{5}} & \ldots & \frac{M_{s}^{2m}H_{0}^{{2m} - 1}}{a_{1,m}k^{{2m} - 1}} \\0 & \frac{M_{s}^{4}H_{0}^{3}}{a_{2,2}k^{3}} & \frac{M_{s}^{6}H_{0}^{5}}{a_{2,3}k^{5}} & \ldots & \frac{M_{s}^{2m}H_{0}^{{2m} - 1}}{a_{2,m}k^{{2m} - 1}} \\\vdots & \ddots & \ddots & \ddots & \vdots \\\vdots & (0) & \ddots & \ddots & \frac{M_{s}^{2m}H_{0}^{{2m} - 1}}{a_{{n - 1},m}k^{{2m} - 1}} \\0 & \ldots & \ldots & \ddots & \frac{M_{s}^{2m}H_{0}^{{2m} - 1}}{a_{n,m}k^{{2m} - 1}}\end{bmatrix},}}$  where M_(s) is effective magnetic moment of amagnetic nanoparticle, k is a Boltzmann's constant, H₀ is an amplitudeof said AC excitation magnetic field, a_(u,v) is a coefficient of anelement at the uth row and the vth column of said coefficient matrix A,where u=1, 2, . . . , n, v=1, 2 . . . , m, and m is a number of Taylor'sexpansion terms, and m≧n; wherein a related column vector Y of saidin-vivo temperature is expressed as ${Y = \begin{bmatrix}\frac{N}{T} \\\frac{N}{T^{3}} \\\vdots \\\frac{N}{T^{{2m} - 1}}\end{bmatrix}},$  where T is said in-vivo temperature of said measuredobject, and N is magnetic nano concentration at said measured object. 8.The in-vivo temperature measurement system of claim 7, wherein saidfifth module comprises: a fifty-first sub-module configured to calculatesaid related column vector of said in-vivo temperature Y=A⁻¹ X, andfurther said in-vivo temperature T=^(2(q-p))√{square root over(Y_(p)/Y_(q))}, 1≦p<q≦2n−1 when the number of said Taylor's expansionterms m is equal to the number of said odd harmonics n, where Y_(p) andY_(q) respectively represents the p^(th) and the q^(th) element of saidrelated column vector Y of said in-vivo temperature; and a fifty-secondsub-module configured to perform least square fitting via B=[N,T]^(T) asa variable and the relationship between said odd harmonics and saidin-vivo temperature X=AY as an objective function whereby determiningsaid in-vivo temperature T when the number of said Taylor's expansionterms m is greater than the number of said odd harmonics n.
 9. Thein-vivo temperature measurement system of claim 7, wherein said fourthmodule is configured to use a digital phase-sensitive detection methodto detect said amplitudes of said odd harmonics, and comprises: aforty-first sub-module configured to sample said AC magnetization signalM of said magnetic nano agent to obtain a discrete intensity signalM(i), where i=1, 2 . . . , L, and L is the number of sampling points; aforty-second sub-module configured to set j=1; a forty-third sub-moduleconfigured to calculate f′=(2j−1)f where f is a frequency of said ACexcitation magnetic field; a forty-fourth sub-module configured togenerate two orthogonal reference signals, and to sample said orthogonalreference signals to obtain two discrete sampling signals R₁(i) andR₂(i); a forty-fifth sub-module configured to determine whether j isequal to 1, to proceed to step (g) if yes, and to proceed to step (f)otherwise; a forty-sixth sub-module configured to filter the 2j−3^(th)odd harmonic in said discrete intensity signal M(i); a forty-seventhsub-module configured to perform mutual correlation calculation and meanfiltering on the discrete sampling signal R₁(i) and said discreteintensity signal M(i) to obtain a first component S_(2j-1), to performmutual correlation calculation and mean filtering on the discretesampling signal R₂(i) and said discrete intensity signal M(i) to obtaina second component O_(2j-1) and to calculate an amplitude of a 2j−1^(th)odd harmonic C_(2j-1)=2√{square root over (S_(2j-1) ²+O_(2j-1) ²)}; anda forty-eighth sub-module configured to determine whether j is less thann, to set j=j+1 and return step (c) if yes, and to end otherwise. 10.The in-vivo temperature measurement system of claim 7, wherein saidfourth module is configured to use a least square system parameteridentification method to detect said amplitudes of said odd harmonics,wherein said fourth module is configured to sample said AC magnetizationsignal M of said magnetic nano agent to obtain a discrete intensitysignal M(i) where i=1, 2 . . . , L, and L is the number of samplingpoints; wherein said fourth module is configured to assume$Z = {\begin{bmatrix}{M(1)} \\{M(2)} \\\vdots \\{M(L)}\end{bmatrix}\mspace{14mu}{and}}$ ${\varphi = \begin{bmatrix}{\sin(\Omega)} & {\sin( {3\Omega} )} & \ldots & {\sin( {( {{2n} - 1} )\Omega} )} \\{\sin( {2\Omega} )} & {\sin( {6\Omega} )} & \ldots & {\sin( {2( {{2n} - 1} )\Omega} )} \\\vdots & \vdots & \ddots & \vdots \\{\sin( {L\;\Omega} )} & {\sin( {3L\;\Omega} )} & \ldots & {\sin( {{L( {{2n} - 1} )}\Omega} )}\end{bmatrix}},$ wherein the fourth module is configured to adjust asampling frequency to find matrices φ and Z so that J=[Z−φX]^(T)[Z−φX]is the minimum, and wherein said fourth module is configured todetermine said column vector X=(φ^(T)φ)⁻¹φ^(T)Z formed by saidamplitudes C_(j) of said odd harmonics, where a digital angularfrequency ${\Omega = \frac{2\pi\; f}{f_{s}}},$  f_(s) represents asampling frequency, π represents a circumference ratio, and asuperscript T represents transpose.